P568: COMPARISON OF VENETOCLAX-BASED INDUCTION THERAPY OR 3 + 7 FOLLOWED BY ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR NEWLY DIAGNOSED AML PATIENTS
Authors: Tran-Der Tan, Lun-Wei Chiou
Journal: HemaSphere (2023)

Background: The current standard treatment for fit newly diagnosed acute myeloid leukemia patients is idarubicin or daunorubicin plus cytarabine (3 + 7 regimen), followed by allogeneic hematopoietic stem cell transplantation. The complete remission rate after induction therapy is between 60% and 80%. About half of them couldenter into allotransplant, and about half could have durable survival. Venetoclax plus azacytidine or low-dose cytarabine is for unfit or elderly AML patients according to VIALE A and VIALE C trials with CR rates up to 60-70% and had less treatment-related adverse effects. Aims: We compared venetoclax-based or 3 + 7 induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation for newly diagnosed AML patients. Methods: We conducted a treatment protocol for newly diagnosed AML patients with venetoclax (100 mg a day) and posaconazole (300 mg a day) according to the pharmacokinetic plus standard dose of cytarabine (100 mg/m2/d x 7 days) or azacytidine (75 mg/m2/d x 7 days) as the induction and consolidation therapy, followed by allogeneic hematopoietic stem cell transplantation for transplant-eligible patients in cohort A, and the same dose of venentoclax and posaconazole plus low dose cytarabine or azacytidine for unfit or non-transplant patients in cohort B between 2019 and 2022. In addition, we compared the outcome with those treated with a 3 + 7 regimen with or without an allogeneic transplant between 2009 and 2018 at our institute in cohort C. Results: Twenty-one patients enrolled in our study between March 2019 and June 2022 with a median age of 56.5 (range 35-77) and 12 male patients. Five patients were therapy-related, and sixteen had specific cytogenetic or gene mutations. In fifteen patients of cohort A, one patient of complex karyotype and double del 17p was refractory to Ven/posa + Ara-C but achieved CR with MRD after FLAG-ida + Ven. CR rate was 93.8%, but two of them got early relapse before transplant in 3 and 6 months after induction therapy, respectively, of whom were MLL e11e3 and inv 3, respectively. Fifteen of 21 underwent allogeneic hematopoietic stem cell transplantation, with a transplant transition rate of 71.4%, with five patients relapsing between +3 and +7 months after allotransplant. One patient died of post-transplant idiopathic pneumonitis without leukemia, and 9 out of 15 patients in leukemia-free survival. Six patients in cohort B, one patient resistant to induction Ven/posa plus LDAC. The total CR rate in our cohorts was 89.5%, and there were 13 patients still in leukemia-free survival until this presentation. The adverse effects of Venetoclax-based therapy included neutropenia and septicemia, anemia, and thrombocytopenia, just like the intensive chemotherapy but remarkably decreased the incidence of oral mucositis, enterocolitis, watery diarrhea, and septicemia. In cohort C with 85 patients treated between 2009 and 2018, the transplant transition rate was 37.34%, and five-year overall survival was 48% and 6% in transplant and non-transplant patients, respectively. Summary/Conclusion: Venetoclax-based induction and consolidation therapy could achieve a high CR rate, far fewer gastrointestinal adverse effects, and a higher transition rate to allotransplant and durable leukemia-free survival.Keywords: Venetoclax, AML, Allogeneic hematopoietic stem cell transplant, Acute myeloid leukemia